Combinatorial-Designed Nano-Platforms to Overcome Tumor Drug Resistance
Development of multidrug resistance (MDR) to conventional and newer generations of anticancer therapeutics is a significant challenge in cancer therapy. MDR is presented clinically as a consequence of many factors that include poor systemic drug delivery efficiency, short residence time, poor permeability into the tumor mass and intracellular availability, as well as micro-environmental selection pressures that give rise to the resistant phenotype.
Drs. Amiji and Duan's innovative strategy to overcome MDR is based on the development of a novel class of biocompatible dextran-based polymeric nano-assembled structures for encapsulation and delivery of small interference RNA (siRNA) that can silence specific genes in resistant cells, specifically mdr-1 and mrp-1 efflux transporters and Bcl-2 and survivin. These constructs will be also used to deliver cytotoxic therapeutic agents, which could induce maximum cell-kill effect in cancer resistant cells.
The goal of this project is to design libraries of nano-assemblies for encapsulation and targeted delivery of siRNA and small molecule anticancer drugs in order to suppress multidrug resistance.